Studies in HIV-infected patients have revealed that serum micronutrient levels are often below normal levels, particularly for vitamins A, B about2, and E, as well as for selenium and zinc. Some studies have correlated low micronutrient levels with more rapid progression of HIV infection. Our initial studies in SIVmac239-infected rhesus monkeys have shown low serum levels of Vitamins B12 and E and selenium. Ongoing studies with a highly supplemented (HS) vitamin/micronutrient intervention in SIV-infected animals show a decrease in the rate of loss of weight and body fat compared to placebo controls. For this competitive renewal, we plan to conduct two phases of investigations: 1) single interventions over 36 months of observation in this SIV- infected model with intramuscular Vitamin B 12 and oral selenium, the two most promising micronutrients in human studies; and 2) Conduct an HS vitamin/micronutrient intervention over 36 months in SIV-infected macaques receiving an antiretroviral regimen of HAART (PMPA, ddI, hydroxyurea), which has been shown to produce undetectable SIV viral loads. Primary end points for both studies are time of death and changes in body weight. Secondary end points are measurements of serum micronutrients; changes in lean body mass (by DEXA, bioelectric impedance [BIA], and somatometric measurements); SIV viral load; CD4 cell count; and development of opportunistic infections. Study 1 will show if a single micronutrient such as B 12 or selenium can produce similar effects on end points as the combined HS preparations. Study 2 will simulate the situation of using HAART in HIV/AIDS patients who may have continued weight loss despite suppression of plasma viral load, in order to see if the HS vitamin/micronutrient intervention can maintain weight and improve nutritional status.